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Biomedical subjects

B Roche

Publications and source records attributed to B Roche.

At least 19 recordsLinked to original sources

Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer.

BACKGROUND: Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response. PURPOSE: Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy. METHODS: The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications. RESULTS: The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

Antimetabolites, Antineoplastic

Functional equivalence in children: derived stimulus-response and stimulus-stimulus relations.

The present study investigated the simultaneous occurrence of emergent stimulus-response relations (functional equivalence) and stimulus-stimulus relations (stimulus equivalence). After being pretrained and tested on two symbolic match-to-sample tasks (X1-Y1, X2-Y2), 20 4- and 5-year-old children were trained to emit specified responses to pairs of stimuli (A1-R1, B1-R1, A2-R2, B2-R2) in one setting (original training) and to emit other responses to one member of each pair (A1-R3, A2-R4) in another setting (reassignment training). Of the 18 children who responded correctly on all trained tasks, 15 emitted the novel responses also in the presence of the nonreassigned stimuli (B1-R3, B2-R4). Eleven of these children also matched same-class stimuli with one another (A1-B1, A2-B2, and vice versa). Additional tests with four of these children documented the formation of conditional response-stimulus relations (R3-B1, R4-B2) in all four children, and of conditional response-response relations (R1-R3, R2-R4, and vice versa) in two of them. Children who did not show stimulus control transfer also failed to match same-class stimuli with one another. Present findings, together with those obtained in animal research, suggest that functional equivalence can imply but does not require stimulus equivalence.

Child, Preschool

De novo and apparent de novo hepatitis B virus infection after liver transplantation.

BACKGROUND/AIMS: The aim of this study was to clarify the aetiology of apparent de novo HBV infection after liver transplantation. METHODS: Twenty out of 570 HBsAg negative patients (3.5%) became HBsAg positive after transplantation and were studied. Donor and recipient sera were retrospectively tested for HBsAg, anti-HBs, anti-HBc, and HBV DNA by PCR. Donor and recipient livers were tested for HBV DNA by PCR on paraffin-embedded tissue. RESULTS: Group 1: HBV infection of donor origin (eight patients): one donor serum was HBsAg positive, three were serum HBV DNA positive, four were liver HBV DNA positive. Group 2: reactivation of latent HBV infection (eight patients) with detection of HBV DNA in pretransplant serum (seven patients) or in native liver (one patient): three were anti-HBs positive, two anti-HBc positive, and three with fulminant hepatitis had no serological HBV markers. Group 3: undetermined origin (four patients) defined by absence of HBV DNA in pretransplant donor and/or recipient sera and liver; however, acquired infection was suspected from two anti-HBs and anti-HBc positive donors. Two patients became HBsAg negative, and five HBV DNA negative. One died from HBV-cirrhosis and two were retransplanted. In the others, the last histology showed cirrhosis (three), chronic hepatitis (nine), acute hepatitis (one), and non-specific change (four patients). CONCLUSIONS: The prevalence of de novo HBV infection in liver transplant patients was 3.5%; the aetiology was determined in 16/20 patients: from the donor in eight, and from the recipient in eight. One should be cautious when donors or recipients are anti-HBc or both anti-HBs and anti-HBc positive.

Adult

A 10.3 kbp segment from nprB to argJ at the 102 degrees region of the Bacillus subtilis chromosome.

The approximately 10 kbp region encompassing nprB and argJ at 102 degrees on the Bacillus subtilis chromosome was sequenced, revealing 12 ORFs, four known genes (argJ, argC, ipi and nprB) and two genes, yitY and yitS, whose products respectively display significant homology with L-gulono-gamma-lactone oxidase of rat and dihydrofolate reductase of Staphylococcus aureus. The data also indicated that nprB mapped to a different position than previously published.

Bacillus subtilis

Sequencing of regions downstream of addA (98 degrees) and citG (289 degrees) in Bacillus subtilis.

The nucleotide sequence of 17.3 kbp downstream of addA (98 degrees) on the Bacillus subtilis chromosome was determined. Twenty putative ORFs were identified. Three of them coincided with known B. subtilis genes, addA, sbcD and wprA. The product of four other ORFs showed similarity to SbcC of Clostridium perfringens, CotH of B. subtilis, 2-hydroxyhepta-2,4-diene-1,7-diodate isomerase of Methanococcus jannaschi and a putative ORF of Pseudomonas syringae. In addition, a sequence of 7.6 kbp downstream of citG (189 degrees) was analysed. Among 10 putative ORFs identified, two coincided with known genes, citG and mrgA, whilst three showed homology with X86780, a sensory protein kinase of Streptomyces hygroscopicus, an alkaline phosphatase regulatory protein and a hypothetical protease, YyxA, of B. subtilis.

Bacillus subtilis

A Bacillus subtilis chromosome segment at the 100 degrees to 102 degrees position encoding 11 membrane proteins.

The 25.9 kbp region upstream of nprB at 100 degrees-102 degrees on the Bacillus subtilis chromosome was sequenced. This revealed a known gene, degA, which was previously mislocated on the genetic map. A total of 29 putative ORFs were identified including a cluster of three ORFs whose products show clear homology with sulphate adenylyl pathway enzymes and, in addition, 11 ORFs whose products have one or more membrane domains, as indicated by their hydropathy profiles.

Bacillus subtilis

A transformation of respondently conditioned stimulus function in accordance with arbitrarily applicable relations.

Adult male subjects saw a sexual film clip paired with a nonsense syllable (C1). Similarly, an emotionally neutral film clip was paired with a second nonsense syllable (C3). Responses to the nonsense syllables were recorded as skin resistance responses. Subjects were also trained in a series of related conditional discriminations, using the C1 and C3 stimuli, from which the following equivalence relations were predicted; A1-B1-C1, A2-B2-C2, and A3-B3-C3. Some subjects were given matching-to-sample (equivalence) tests after the conditional discrimination training (Experiment 1), whereas others were not (Experiment 2). Subjects were tested for a transformation of eliciting functions by presenting the A1 and A3 stimuli, which were related through equivalence to C1 and C3, respectively. Five of the 6 subjects who showed significantly greater conditioned responses to C1 than to C3, also showed significantly greater skin resistance responses to A1 than to A3. Two additional subjects demonstrated a transformation of an eliciting stimulus function in accordance with five-member equivalence relations (Experiment 3), and another 5 subjects demonstrated similar effects in accordance with the relations of sameness and opposition (Experiment 4).

Adolescent

Tailgut Cyst, an unusual evolution.

Developmental Tailgut Cyst (TGC) arise in the presacrococcygeal space. Most of these cysts are discovered during rectal examination. They may be the source of chronic perirectal symptoms but rarely undergo malignant change. There is a female predominance and TGC may grow to a considerable size. Biopsy and drainage lead to recurrence and infection. TGC, even when asymptomatic, should be totally excised.

Adult

Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma.

BACKGROUND: Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE: We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS: Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS: Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS: The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Aged

[Pelvic pain of proctological origin].

Pelvic pain of anorectal origin should be carefully investigated. The detailed clinical history may be sufficient to establish diagnosis and determine the etiology of anorectal pain. The diagnosis should be confirmed by complementary clinical investigations. The diagnosis of essential anorectal pain can be established only after failure of measures instituted to correct organic lesions and if pain persists. Among types of essential anorectal pain, coccygodinia and nervus pudendus entrapment are responsive to precise and effective management.

Adult

The value of early transjugular liver biopsy after liver transplantation.

Conventional percutaneous liver biopsy in the early postoperative period, within 30 days, following liver transplantation may be impossible due to coagulopathy and/or ascites. The use of transjugular liver graft biopsy (TJLB) in this setting is an attractive alternative in that a tissue diagnosis can be obtained despite the relative contraindications for percutaneous biopsy during this period. During the early posttransplant period, 124 TJLBs were performed in 105 liver patients, the majority (89%) of whom had standard liver transplantation without preservation of the native inferior vena cava; the others (11%) had the native inferior vena cava intact. The technical success rate was 87%, with adequate specimen for definitive diagnosis in most instances (86%), which included both rejection (61%) and nonrejection (39%) diagnoses on final histopathology. The biopsy diagnosis influenced clinical management in the majority of cases (65%), with decisions made to perform retransplantation (3%), to influence initiation of antirejection therapy (59%), and to institute antiviral therapy (3%). There was no morbidity or mortality associated with TJLB and it is feasible, safe, and effective in the early period after liver transplantation.

Biopsy, Needle

Application of formaldehyde for treatment of hemorrhagic radiation-induced proctitis.

Radiation-induced proctitis with hemorrhage is not a common complication of radiotherapy to the pelvis for carcinoma. In the most severe forms, massive hemorrhage may necessitate repeated transfusions and inpatient treatment. In severe cases medical treatment has not been proved effective. Surgery may lead to serious complications and is technically difficult. Six patients who showed a hemorrhagic radiation-induced proctitis have been treated as outpatients with application of formaldehyde 4%. In four cases the bleeding ceased after the first formaldehyde application; two patients continued to bleed, but another application of formaldehyde 3 weeks later definitively controlled the hemorrhage. Follow-up evaluation at 12 months showed in each case that the hemorrhage was controlled and treated. There were no complications, such as burns or late stenoses of the deep layers of the rectum. This inexpensive technique is well tolerated by the patient, gives good long-term results, and is available at every hospital. Local application of formaldehyde 4% to the rectum may be the treatment of choice for hemorrhagic radiation-induced proctitis.

Administration, Topical

Gallstones in chronic spinal cord injury: is impaired gallbladder emptying a risk factor?

OBJECTIVE: To confirm that spinal cord injured persons are susceptible to gallstones and to evaluate the role of gallbladder stasis as a risk factor. STUDY DESIGN: Twenty-nine subjects with chronic spinal cord injury underwent fasting ultrasonography to determine the incidence of gallstones and to quantitate gallbladder emptying response to a 20g fat liquid meal. Gallbladder emptying fraction was compared to that of healthy subjects studied concurrently. RESULTS: Gallstones or sludge were found in 6 spinal cord injured men, a minimal prevalence of 21%. Four additional subjects had prior cholecystectomy for stones, giving a potential maximal prevalence of 30%. Four of the 6 subjects had gallstone risk factors of diabetes, obesity, and/or family history. Gallbladder stasis was not apparent in chronic spinal cord injured subjects. Only 5 subjects had poor gallbladder emptying, and 4 of them had diabetes and/or obesity. CONCLUSIONS: The study confirms an increased prevalence of gallstones after spinal cord injury. However, gallbladder stasis did not appear to be etiologic, and most gallstones were associated with conventional risk factors. The results do not support a general policy of gallstone screening or prophylactic therapy after spinal cord injury.

Adult

Injection drug use and risk of HIV transmission among homeless men with mental illness.

OBJECTIVE: The high seroprevalence of HIV that has been reported among homeless individuals with mental illness indicates an urgent need to examine HIV risk behavior in this population. METHOD: Injection drug use and sexual behavior were assessed in comprehensive interviews with 218 homeless mentally ill men in a New York City shelter. First, the proportion of men who had injected drugs was established. Then, among those who had injected drugs, the injection drug use behaviors associated with HIV transmission (i.e., whether they had ever engaged in high-risk behaviors and had ever engaged in risk-reduction behaviors) and their current sexual risk behaviors were examined. RESULTS: Fifty (23%) of the 218 men had injected drugs. Among these 50, the great majority had engaged in high-risk behaviors, including sharing needles (66%) and using shooting galleries (64%). Few had engaged in risk-reduction behaviors, such as cleaning needles with bleach (22%) and using a needle exchange program (2%). In the past 6 months alone, the majority of the injection drug users had had unprotected sex with women (48%) or with men (10%). CONCLUSIONS: This study documents a high lifetime prevalence of injection drug use in a group of homeless men with mental illness. The men who had injected drugs reported injection drug use and sexual behaviors with high risk of HIV transmission and gave scant evidence of risk-reduction behaviors. These individuals may fall between service systems and may be difficult to reach but, nonetheless, must be included in efforts to prevent transmission of HIV infection.

Adult

[Value of endo-anal ultrasonography in the assessment of anal incontinence].

Endoanal ultrasonography with a Brüel and Kjaer 7 mHz rotative probe allows precise evaluation of the different structures of the anus, the anal canal and the rectum. The integrity, thickness and length of the muscle layers can be measured in a reproducible way during contracture and at rest. In addition to the classic images, video recording can be carried out. We examined 96 consecutive patients with anal incontinence, comprising 82 female and 14 male patients. In 76 cases the origin were an obstetrical lesion, 7 were surgical lesions, in 9 cases the lesion was posttraumatic and in 2 cases a malformation. In 2 cases a rectal prolapse was associated. We found that endoanal ultrasonography permits a precise diagnosis of anal incontinence. The nature and the extent of sphincteric lesions can be determined and the surgical procedure can thus be planned. In the absence of organic lesions this examination serves to avoid unnecessary surgical treatment.

Adult